PHARMACOLOGY: Flunixin meglumine is a potent, non-narcotic, nonsteroidal,
analgesic agent with anti-inflammatory and antipyretic activity. It is significantly
more potent than pentazocine, meperidine, and codeine as an analgesic in the
rat yeast paw test.

Horse: Flunixin is four times as potent on a mg-per-mg basis as phenylbutazone
as measured by the reduction in lameness and swelling in the horse. Plasma half-life
in horse serum is 1.6 hours following a single dose of 1.1 mg/kg. Measurable
amounts are detectable in horse plasma at 8 hours postinjection.

Cattle: Flunixin meglumine is a weak acid (pKa=5.82)1 which exhibits
a high degree of plasma protein binding (approximately 99%).2 However, free
(unbound) drug appears to readily partition into body tissues (VSS predictions
range from 297 to 782 mL/kg.2-5 Total body water is approximately equal to 570
mL/kg).6 In cattle, elimination occurs primarily through biliary excretion.7
This may, at least in part, explain the presence of multiple peaks in the blood
concentration/time profile following IV administration.2

In healthy cattle, total body clearance has been reported to range from 90
to 151 mL/kg/hr.2-5 These studies also report a large discrepancy between the
volume of distribution at steady state (VSS) and the volume of distribution
associated with the terminal elimination phase (Vß). This discrepancy
appears to be attributable to extended drug elimination from a deep compartment.8
The terminal half-life has been shown to vary from 3.14 to 8.12 hours.2-5

Flunixin persists in inflammatory tissues9 and is associated with anti-inflammatory
properties which extend well beyond the period associated with detectable plasma
drug concentrations.4,9 These observations account for the counterclockwise
hysteresis associated with flunixin's pharmacokinetic/pharmacodynamic relationships.10

Therefore, prediction of drug concentrations based upon the estimated plasma
terminal elimination half-life will likely underestimate both the duration of
drug action and the concentration of drug remaining at the site of activity.

INDICATIONS: Horse: BANAMINE Injectable Solution is recommended for
the alleviation of inflammation and pain associated with musculoskeletal disorders
in the horse. It is also recommended for the alleviation of visceral pain associated
with colic in the horse.

Cattle: BANAMINE Injectable Solution is indicated for the control of
pyrexia associated with bovine respiratory disease and endotoxemia and acute
bovine mastitis. BANAMINE Injectable Solution is also indicated for the control
of inflammation in endotoxemia.

DOSE AND ADMINISTRATION: Horse: The recommended dose for musculoskeletal
disorders is 0.5 mg per pound (1 mL/100 lbs) of body weight once daily. Treatment
may be given by intravenous or intramuscular injection and repeated for up to
5 days. Studies show onset of activity is within 2 hours. Peak response occurs
between 12 and 16 hours and duration of activity is 24-36 hours.

The recommended dose for the alleviation of pain associated with equine colic
is 0.5 mg per pound of body weight. Intravenous administration is recommended
for prompt relief. Clinical studies show pain is alleviated in less than 15
minutes in many cases. Treatment may be repeated when signs of colic recur.
During clinical studies approximately 10% of the horses required one or two
additional treatments. The cause of colic should be determined and treated with
concomitant therapy.

Cattle: The recommended dose for control of pyrexia associated with
bovine respiratory disease and endotoxemia and control of inflammation in endotoxemia,
is 1.1 to 2.2 mg/kg (0.5 to 1 mg/lb; 1 to 2 mL per 100 lbs) of body weight given
by slow intravenous administration either once a day as a single dose or divided
into two doses administered at 12-hour intervals for up to 3 days. The total
daily dose should not exceed 2.2 mg/kg (1.0 mg/lb) of body weight. Avoid rapid
intravenous administration of the drug.

The recommended dose for acute bovine mastitis is 2.2 mg/kg (1 mg/lb; 2mL per
100 lbs) of body weight given once by intravenous administration.

CONTRAINDICATIONS:

Horse: There are no known contraindications to this drug when used as
directed. Intra-arterial injection should be avoided. Horses inadvertently injected
intra-arterially can show adverse reactions. Signs can be ataxia, incoordination,
hyperventilation, hysteria, and muscle weakness. Signs are transient and disappear
without antidotal medication within a few minutes. Do not use in horses showing
hypersensitivity to flunixin meglumine.

Cattle: There are no known contraindications to this drug in cattle
when used as directed. Do not use in animals showing hypersensitivity to flunixin
meglumine. Use judiciously when renal impairment or gastric ulceration are suspected.

RESIDUE WARNINGS: Cattle must not be slaughtered for human consumption
within 4 days of the last treatment. Milk that has been taken during treatment
and for 36 hours after the last treatment must not be used for food. Not for
use in dry dairy cows. A withdrawal period has not been established for this
product in preruminating calves. Do not use in calves to be processed for veal.
Not for use in horses intended for food.

PRECAUTIONS: As a class, cyclo-oxygenase inhibitory NSAIDs may be associated
with gastrointestinal and renal toxicity. Sensitivity to drug-associated adverse
effects varies with the individual patient. Patients at greatest risk for renal
toxicity are those that are dehydrated, on concomitant diuretic therapy, or
those with renal, cardiovascular, and/or hepatic dysfunction.

Since many NSAIDs possess the potential to induce gastrointestinal ulceration,
concomitant use of BANAMINE Injectable Solution with other anti-inflammatory
drugs, such as other NSAIDs and corticosteroids, should be avoided or closely
monitored.

Horse: The effect of BANAMINE Injectable Solution on pregnancy has not
been determined. Studies to determine the activity of BANAMINE Injectable Solution
when administered concomitantly with other drugs have not been conducted. Drug
compatibility should be monitored closely in patients requiring adjunctive therapy.

Cattle: Do not use in bulls intended for breeding, as reproductive effects
of BANAMINE Injectable Solution in these classes of cattle have not been investigated.
NSAIDs are known to have potential effects on both parturition and the estrous
cycle. There may be a delay in the onset of estrus if flunixin is administered
during the prostaglandin phase of the estrous cycle. The effects of flunixin
on imminent parturition have not been evaluated in a controlled study. NSAIDs
are known to have the potential to delay parturition through a tocolytic effect.
Do not exceed the recommended dose.

SAFETY: Horse: A 3-fold intramuscular dose of 1.5 mg/lb of body weight
daily for 10 consecutive days was safe. No changes were observed in hematology,
serum chemistry, or urinalysis values. Intravenous dosages of 0.5 mg/lb daily
for 15 days; 1.5 mg/lb daily for 10 days; and 2.5 mg/lb daily for 5 days produced
no changes in blood or urine parameters. No injection site irritation was observed
following intramuscular injection of the 0.5 mg/lb recommended dose. Some irritation
was observed following a 3-fold dose administered intramuscularly.

Cattle: No flunixin-related changes (adverse reactions) were noted in
cattle administered a 1X (2.2 mg/kg; 1.0 mg/lb) dose for 9 days (three times
the maximum clinical duration). Minimal toxicity manifested itself at moderately
elevated doses (3X and 5X) when flunixin was administered daily for 9 days,
with occasional findings of blood in the feces and/or urine. Discontinue use
if hematuria or fecal blood are observed.

ADVERSE REACTIONS: In horses, isolated reports of local reactions following
intramuscular injection, particularly in the neck, have been received. These
include localized swelling, sweating, induration, and stiffness. In rare instances
in horses, fatal or nonfatal clostridial infections or other infections have
been reported in association with intramuscular use of BANAMINE Injectable Solution.
In horses and cattle, rare instances of anaphylactic-like reactions, some of
which have been fatal, have been reported, primarily following intravenous use.

HOW SUPPLIED: BANAMINE Injectable Solution, 50 mg/mL, is available in
50-mL, 100-mL, and 250-mL multi-dose vials.